Androgens are steroid hormones found circulating at varying levels in both men and women. They are essential in sex differentiation, development, and reproductive function. However, androgens can also play a role in undesirable physiological conditions, including different types of baldness.
One of the most prevalent types of baldness is male pattern baldness (MPB). This condition is widespread, affecting two of every three men. MPB, which is inherited as a autosomal dominant trait with partial penetrance, is known to be androgen-dependent. This is evidenced in the fact that castrated males do not develop baldness.
Hair follicles initially appear in utero. No new follicles are created after birth, and it is believed that none are lost in adult life. However, in MPB, hair follicles do become progressively smaller (miniaturized). Hair follicles exhibit cyclic activity. Each period of active growth of hair (anagen) alternates with a resting period (telogen), separated by a relatively short transition phase (catagen). Hair growth on the human scalp is a mosaic of follicular activity with each follicle at a stage independent of its neighbors. At any one time, between 4-24% (average 13%) of follicles are in telogen and &lt;1% in catagen. Hairs reach a terminal or definitive length, which depends mainly on the duration of anagen, and partly on the rate of growth. In the human scalp, anagen may occupy three years or more; however, the percentage of follicles in telogen increases with age, resulting in a gradual thinning. In MPB, the ratio of telogen to anagen is increased still further. Also, in MPB the hairs in affected areas become steadily shorter and finer, and ultimately may be reduced to the short (&lt;2 cm), fine, unpigmented hair known as vellus hair.
Although the endocrine system does not directly initiate or curtail the activity of the hair follicle, androgens do accelerate or retard the normal cyclic activity of hair growth described above.
Testosterone (T) is the major circulating androgen. Because circulating T is largely bound to sex hormone binding globulin (SHBG), the availability of T depends not only on its total concentration, but also on the level of SHBG. While plasma T levels in MPB appear to be normal, SHBG levels tend to be low. This implies that bald males may have higher levels of free testosterone. This implication is borne out by the demonstration that bald males have high T concentrations in their saliva.
T itself has minimal activity in the hair follicle. A much more active metabolite which is believed to be responsible for MPB is 5-alpha-dihydrotestosterone (DHT). DHT is formed in the cytoplasm of hair follicle cells after reduction of T by the enzyme 5-alpha-reductase. Because balding men have increased 5-alpha-reductase activity in the hair follicles and skin of the frontal scalp, it has been suggested that this enzyme may be involved in development of MPB. Two genes have been reported, each of which codes for a distinct 5-alpha-reductase enzyme (Genbank locus:HUM5AR and HUMSRDA).
The effects of androgens in MPB are mediated by the binding of an androgen (primarily DHT) to the androgen receptor (AR). Androgens bind specifically to the AR, which is either situated in the nucleus or transferred to it from the cytoplasm. The AR belongs to a subfamily of steroid/thyroid hormone/retinoic acid receptors, whose activity is controlled by the tight and specific binding of the cognate ligand. Evidence for the involvement of the AR in MPB includes the demonstration that androgenic alopecia (a type of pattern baldness in women) can be alleviated by treatment with antiandrogens. These antiandrogens, such as spironolactone, cyproterone acetate, flutamide and cimetidine, bind to the AR and competitively inhibit DHT binding. In addition, sebaceous glands of bald scalps were found to have greater binding affinity and capacity for androgens than those in hairy scalps.
In the past, baldness was treated only with surgical procedures, such as hair transplants and scalp reduction. Recently, however, there have been some advances in medical treatment of baldness. The most publicized of these is minoxidil (Rogaine.TM.). Minoxidil is a potent vasodilator which has been used as a treatment for hypertension. A noted side effect of this treatment was the growth of hair on parts of the body. This led to the testing of topical minoxidil on balding areas of the scalp. The result in some cases was an apparent decrease in vellus hairs with a concomitant increase in terminal hairs. Many of the subjects studied reported that their rate of hair loss decreased. However, not all subjects responded to treatment with minoxidil. It was found that younger men who only recently (within five years) had begun to bald responded better than older men, and that minoxidil worked best on small areas of vertex baldness.
Research indicates that minoxidil will not help the majority of balding men, although it does help a specific population of minimally balding young men. The reason for the effectiveness of minoxidil is not known. It might be due to an increase in blood flow caused by the vasodilating effect of the drug. The longterm effects of minoxidil treatment are not known.
Other treatments are directed at reducing the production of DHT from testosterone, thereby preventing its cytosol-nuclear binding and/or translocation. Topical or intralesional progesterone can also be used to reduce the production of DHT from T. Since progesterone is similar in structure to testosterone, it competes with testosterone for 5-alpha-reductase, the enzyme that converts testosterone to DHT.